The goal is to develop improved diagnostic imaging agents for human melanoma based on a radio-labeled monoclonal antibody. P97 and HMW are oncofetal antigens present on human melanoma tumor cells. Studies in nude mice have shown there is active concentration of both antibodies (and Fab fragments) directed against these antigens of human melanoma. Tumor labeling is antigen specific, as documented by comparisons with radiolabeled control immunoglobulin and immune fragments. Patients have been studied with whole antibody and fragments, and uptake has been documented in metastatic lesions. About 80% of documented metastatic lesions have been imaged, and antigen-specific uptake in tumor has been documented by comparison to radiolabeled control immunoglobulin. Maximum target-to-nontarget ratios observed from human tumors, biopsied at 72 hrs after intravenous administration of antibody, were 7 to 1. Fifty-five patients with advanced malignant melanoma have been studied. In addition, antibody imaging of metastatic melanoma in lymph nodes (immunolymphoseintigraphy) has begun. Antibody fragments are injected subcutaneously. In this case diseased nodes show both specific and non-specific localization of murine immunoglobulin. We are studying the details of antibody radiolabeling methods and have determined optimum conditions for preserving the immunoreactivity of labeled antibodies in relation to iodine/antibody molar ratios and all other reaction conditions, and have designed techniques to minimize radiolysis of final product. We are beginning work with antibody directed against non-small cell carcinoma of the lung. (2)